Inflammation Class Notes PDF

NURS 7053 Advanced Pathophysiology I for DNP Students Inflammation - Class Notes Inflammation Purpose of Inflammation Destroy infectious and inju...

NURS 7053 Advanced Pathophysiology I for DNP Students Inflammation - Class Notes Inflammation Purpose of Inflammation Destroy infectious and injurious organisms Wall off the site of infection to limit the damage Stimulate and enhance the immune response Stimulate tissue healing and provide a framework for tissue repair Characteristics of the Inflammatory Response Occurs in vascular tissues Immediate Nonspecific No memory Inflammatory chemicals (mediators) will affect anything, host & non-host Self-limiting Overview of the Components of the Inflammatory Response Cells: White blood cells (WBCs), endothelial cells, and platelets Inflammatory chemicals: Cytokines, vasoactive inflammatory mediators, and anti-inflammatory mediators Plasma protein systems: Complement, clotting and kinin systems 1  NURS 7053 Advanced Pathophysiology I for DNP Students Inflammation - Class Notes Activation of the Inflammatory Response Trauma to the cell membrane Hypoxic injury (examples: myocardial infarction, stroke) Chemical injury (examples: aspiration of gastric fluid in lungs, peptic ulcer disease, pancreatitis) Immune injury (examples: autoimmune disease, allergic reactions) Infection Thermal injury (i.e., burns) Ionizing radiation Overview of Inflammatory Response to Cell Injury Mast cell degranulation and release of initial vasoactive mediators (e.g., histamine) White blood cell margination and migration Release of cytokines and inflammatory mediators Activation of the plasma protein systems 2  NURS 7053 Advanced Pathophysiology I for DNP Students Inflammation - Class Notes Cells of Inflammation and Inflammatory Mediators Mast Cell Most important activator of the local inflammatory response Location Activators Local cellular injury Endotoxin Complement proteins Immunologic factors: IgE hypersensitivity Function Degranulation: release of preformed chemicals Histamine - vasodilation - increased capillary permeability - non-vascular smooth muscle contraction 3  NURS 7053 Advanced Pathophysiology I for DNP Students Inflammation - Class Notes Notes on histamine receptors (location + action) H1 receptors (promote inflammation) Arterial smooth muscle – vasodilation Endothelial cells – endothelial cell retraction/increased capillary permeability Bronchial smooth muscle – bronconstriction WBCs – chemotaxis Mast cells – more degranulation H2 receptors (inhibit inflammation + other actions) Mast cells – inhibits degranulation WBCs – inhibits chemotaxis Parietal and chief cells lining stomach – HCl and gastric enzyme secretion Synthesis of mediators: arachadonic acid (AA) metabolites Leukotrienes – actions are same as histamine Prostaglandins (PgE 2) – actions are same as histamine + pain 4  NURS 7053 Advanced Pathophysiology I for DNP Students Inflammation - Class Notes Basophils Normal range: 0.4-1.0% of total WBC count Function Similar to mast cells - release histamine and leukotrienes in bloodstream Also release heparin Neutrophils - Polymorphic neutrophils (a.k.a. PMNs, segs, polys) Normal range: 45-73% of total WBC count Immature neutrophils are called bands or stabs Normal range: 3-5% of total WBC count Function Arrive during acute phases of inflammation (6-12 hours after degranulation) Activated by proinflammatory cytokines (e.g., IL-1 and TNF-alpha) Phagocytosis of bacteria and debris – destruction of cells via lysosomal or free radical injury Release of inflammatory mediators: more cytokines (interleukins, TNF), platelet activating factor, AA metabolites, etc 5  NURS 7053 Advanced Pathophysiology I for DNP Students Inflammation - Class Notes Eosinophils Normal range: 1-3% of total WBC count Functions Release chemicals that control inflammation (example: histamine and leukotrienes are inactivated by histaminase and arylsulfatase released by eosinophils) Phagocytosis of parasites Involved in allergic responses (type I hypersensitivities) Phagocytosis of bacteria and yeast (less important role) Monocytes/Macrophages Normal range for monocytes: 4-6% of total WBC count Released into bloodstream by the bone marrow as a monocyte Migrate to inflammatory site and transform into a macrophage (triggered by proinflammatory cytokines) Many tissues have residential macrophages (liver, spleen, lungs, lymph nodes...) 6  NURS 7053 Advanced Pathophysiology I for DNP Students Inflammation - Class Notes Functions Process antigen (activates the immune repsonse) Phagocytosis of bacteria and debris Release of inflammatory mediators: interleukins, tumor necrosis factor, free radicals, platelet activating factor, proteases, AA metabolites Promote wound healing by activating fibroblasts, stimulating angiogenesis, and releasing growth factors Other cells involved in inflammation Platelets Functions in Inflammation Work with coagulation proteins to stop bleeding Release approximately 35 other biochemical mediators Serotonin - vasoconstriction Platelet activating factor (PAF) - vasodilation, increased capillary permeability, bronchoconstriction 7  NURS 7053 Advanced Pathophysiology I for DNP Students Inflammation - Class Notes Endothelial Cells Functions in inflammation Increased capillary permeability Express adhesion molecules to guide white blood cells to area of injury Secretion of vasoactive mediators (nitric oxide, PAF, prostaglandins, etc...) Nitric oxide (a.k.a. endothelium-derived relaxation factor (EDRF)) Potent vasodilator Also a free radical The Plasma Proteins of Inflammation Inflammation is mediated by three plasma protein systems: The complements system, clotting system, and kinin system. Each system consists of a series of inactive plasma proteins known as proenzymes. When the first proenzyme in a system is activated, it initiates a cascade in which the next proenzyme in the series becomes activated. The end products of each system serve as inflammatory mediators that promote (or in some cases inhibit) inflammation. Complement System 10+ proteins = 10% of plasma proteins; pathways converge at C3 Classical Pathway Activation – Presence of antigen-antibody (Ag-Ab) complexes (IgG or IgM complexes only) Alternate Pathway Activation – C3b binds to microbe cell membrane Lectin pathway Activation – Binding of mannose-binding lectin (MBL) to microbe cell membranes 8  NURS 7053 Advanced Pathophysiology I for DNP Students Inflammation - Class Notes Function of activated complement proteins C2a, C3a, C5a: vasodilation, increased capillary permeability, bronchoconstriction C2, C3, C3b, C4, C5: opsonization C3a and C5a: chemotaxis C5 through C9 (membrane attack complex): bacterial (and other) cell lysis 9  NURS 7053 Advanced Pathophysiology I for DNP Students Inflammation - Class Notes Clotting System Sequential activation of a series of clotting factors resulting in the production of fibrin. Extrinsic and Intrinsic Pathways Functions of fibrin Forms a meshwork to stop bleeding Limits infection Forms framework for scar tissue formation 10  NURS 7053 Advanced Pathophysiology I for DNP Students Inflammation - Class Notes Kinin System Functions of Bradykinin Works later and more slowly than histamine Vasodilation & increased capillary permeability Bronchoconstriction Induces pain Local Manifestations of Inflammation Heat & Redness Pain Edema/Swelling Loss of function 11  NURS 7053 Advanced Pathophysiology I for DNP Students Inflammation - Class Notes Systemic Manifestations of Acute Inflammation Fever: caused by endotoxin, interleukin (IL-1), tumor necrosis factor (TNF), prostaglandins Leukocytosis: stimulated by granulocyte colony stimulating growth factors (GCSF) from macrophages Increased in neutrophils (typically see 70-85% PMNs) Increased in bands (typically see 10-20% bands) Increased circulating plasma proteins – ‘Acute phase reactants’ Release by liver in response to fever, IL-1 Inflammatory/clotting proteins: Fibrinogen, prothrombin, complement proteins, etc Other liver proteins: Ferritin *C-reactive protein (normal < 1 mg/dL, with bacterial infection see > 10 mg/dL) Low albumin/pre-albumin Increased erythrocyte sedimentation rate (ESR) When plasma protein levels in the plasma are elevated (e.g., acute phase reactants released during inflammation), RBCs aggregate and precipitate rapidly 12